Determination of the ED95 of a single bolus dose of dexmedetomidine for adequate sedation in obese or nonobese children and adolescents

Abstract

Background: With the increasing prevalence of children who are overweight and with obesity, anaesthesiologists must determine the optimal dosing of medications given the altered pharmacokinetics and pharmacodynamics in this population. We therefore determined the single dose of dexmedetomidine that provided sufficient sedation in 95% (ED₉₅) of children with and without obesity as measured by a minimum Ramsay sedation score (RSS) of 4.

Methods: Forty children with obesity (BMI >95th percentile for age and gender) and 40 children with normal weight (BMI 25th-84th percentile), aged 3-17 yr, ASA physical status 1-2, undergoing elective surgery, were recruited. The biased coin design was used to determine the target dose. Positive responses were defined as achievement of adequate sedation (RSS ≥4). The initial dose for both groups was dexmedetomidine 0.3 μg kg^-1 i.v. infusion for 10 min. An increment or decrement of 0.1 μg kg^-1 was used depending on the responses. Isotonic regression and bootstrapping methods were used to determine the ED₉₅ and 95% confidence intervals (CIs), respectively.

Results: The ED₉₅ of dexmedetomidine for adequate sedation in children with obesity was 0.75 μg kg^-1 with 95% CI of 0.638-0.780 μg kg^-1, overlapping the CI of the ED₉₅ estimate of 0.74 μg kg^-1 (95% CI: 0.598-0.779 μg kg^-1) for their normal-weight peers.

Conclusions: The ED₉₅ values of dexmedetomidine administered over 10 min were 0.75 and 0.74 μg kg^-1 in paediatric subjects with and without obesity, respectively, based on total body weight.

Clinical trial registration: ChiCTR1800014266.

Keywords: biased coin design; body mass index; dexmedetomidine i.v.; obesity; paediatric patients; sedation.